Addressing challenges in low-income and middle-income countries through novel radiotherapy research opportunities.

Although radiotherapy continues to evolve as a mainstay of the oncological armamentarium, research and innovation in radiotherapy in low-income and middle-income countries (LMICs) faces challenges. This third Series paper examines the current state of LMIC radiotherapy research and provides new data from a 2022 survey undertaken by the International Atomic Energy Agency and new data on funding. In the context of LMIC-related challenges and impediments, we explore several developments and advances-such as deep phenotyping, real-time targeting, and artificial intelligence-to flag specific opportunities with applicability and relevance for resource-constrained settings. Given the pressing nature of cancer in LMICs, we also highlight some best practices and address the broader need to develop the research workforce of the future. This Series paper thereby serves as a resource for radiation professionals.

Changes in serial multiparametric MRI and FDG-PET/CT functional imaging during radiation therapy can predict treatment response in patients with head and neck cancer.

OBJECTIVES: To test if tumour changes measured using combination of diffusion-weighted imaging (DWI) MRI and FDG-PET/CT performed serially during radiotherapy (RT) in mucosal head and neck carcinoma can predict treatment response. METHODS: Fifty-five patients from two prospective imaging biomarker studies were analysed. FDG-PET/CT was performed at baseline, during RT (week 3), and post RT (3 months). DWI was performed at baseline, during RT (weeks 2, 3, 5, 6), and post RT (1 and 3 months). The ADCmean from DWI and FDG-PET parameters SUVmax, SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were measured. Absolute and relative change (%∆) in DWI and PET parameters were correlated to 1-year local recurrence. Patients were categorised into favourable, mixed, and unfavourable imaging response using optimal cut-off (OC) values of DWI and FDG-PET parameters and correlated to local control. RESULTS: The 1-year local, regional, and distant recurrence rates were 18.2% (10/55), 7.3% (4/55), and 12.7% (7/55), respectively. ∆Week 3 ADCmean (AUC 0.825, p = 0.003; OC ∆ > 24.4%) and ∆MTV (AUC 0.833, p = 0.001; OC ∆ > 50.4%) were the best predictors of local recurrence. Week 3 was the optimal time point for assessing DWI imaging response. Using a combination of ∆ADCmean and ∆MTV improved the strength of correlation to local recurrence (p ≤ 0.001). In patients who underwent both week 3 MRI and FDG-PET/CT, significant differences in local recurrence rates were seen between patients with favourable (0%), mixed (17%), and unfavourable (78%) combined imaging response. CONCLUSIONS: Changes in mid-treatment DWI and FDG-PET/CT imaging can predict treatment response and could be utilised in the design of future adaptive clinical trials. CLINICAL RELEVANCE STATEMENT: Our study shows the complementary information provided by two functional imaging modalities for mid-treatment response prediction in patients with head and neck cancer. KEY POINTS: •FDG-PET/CT and DWI MRI changes in tumour during radiotherapy in head and neck cancer can predict treatment response. •Combination of FDG-PET/CT and DWI parameters improved correlation to clinical outcome. •Week 3 was the optimal time point for DWI MRI imaging response assessment.

Comparison between [68Ga]Ga-PSMA-617 and [18F]FET PET as Imaging Biomarkers in Adult Recurrent Glioblastoma.

The aim of this prospective clinical study was to evaluate the potential of the prostate specific membrane antigen (PSMA) targeting ligand, [68Ga]-PSMA-Glu-NH-CO-NH-Lys-2-naphthyl-L-Ala-cyclohexane-DOTA ([68Ga]Ga-PSMA-617) as a positron emission tomography (PET) imaging biomarker in recurrent glioblastoma patients. Patients underwent [68Ga]Ga-PSMA-617 and O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET) PET scans on two separate days. [68Ga]Ga-PSMA-617 tumour selectivity was assessed by comparing tumour volume delineation and by assessing the intra-patient correlation between tumour uptake on [68Ga]Ga-PSMA-617 and [18F]FET PET images. [68Ga]Ga-PSMA-617 tumour specificity was evaluated by comparing its tumour-to-brain ratio (TBR) with [18F]FET TBR and its tumour volume with the magnetic resonance imaging (MRI) contrast-enhancing (CE) tumour volume. Ten patients were recruited in this study. [68Ga]Ga-PSMA-617-avid tumour volume was larger than the [18F]FET tumour volume (p = 0.063). There was a positive intra-patient correlation (median Pearson r = 0.51; p < 0.0001) between [68Ga]Ga-PSMA-617 and [18F]FET in the tumour volume. [68Ga]Ga-PSMA-617 had significantly higher TBR (p = 0.002) than [18F]FET. The [68Ga]Ga-PSMA-617-avid tumour volume was larger than the CE tumour volume (p = 0.0039). Overall, accumulation of [68Ga]-Ga-PSMA-617 beyond [18F]FET-avid tumour regions suggests the presence of neoangiogenesis in tumour regions that are not overly metabolically active yet. Higher tumour specificity suggests that [68Ga]-Ga-PSMA-617 could be a better imaging biomarker for recurrent tumour delineation and secondary treatment planning than [18F]FET and CE MRI.

A systematic review of assessment approaches to predict opioid misuse in people with cancer.

CONTEXT: Cancer prevalence is increasing, with many patients requiring opioid analgesia. Clinicians need to ensure patients receive adequate pain relief. However, opioid misuse is widespread, and cancer patients are at risk. OBJECTIVES: This study aims (1) to identify screening approaches that have been used to assess and monitor risk of opioid misuse in patients with cancer; (2) to compare the prevalence of risk estimated by each of these screening approaches; and (3) to compare risk factors among demographic and clinical variables associated with a positive screen on each of the approaches. METHODS: Medline, Cochrane Controlled Trial Register, PubMed, PsycINFO, and Embase databases were searched for articles reporting opioid misuse screening in cancer patients, along with handsearching the reference list of included articles. Bias was assessed using tools from the Joanna Briggs Suite. RESULTS: Eighteen studies met the eligibility criteria, evaluating seven approaches: Urine Drug Test (UDT) (n = 8); the Screener and Opioid Assessment for Patients with Pain (SOAPP) and two variants, Revised and Short Form (n = 6); the Cut-down, Annoyed, Guilty, Eye-opener (CAGE) tool and one variant, Adapted to Include Drugs (n = 6); the Opioid Risk Tool (ORT) (n = 4); Prescription Monitoring Program (PMP) (n = 3); the Screen for Opioid-Associated Aberrant Behavior Risk (SOABR) (n = 1); and structured/specialist interviews (n = 1). Eight studies compared two or more approaches. The rates of risk of opioid misuse in the studied populations ranged from 6 to 65%, acknowledging that estimates are likely to have varied partly because of how specific to opioids the screening approaches were and whether a single or multi-step approach was used. UDT prompted by an intervention or observation of aberrant opioid behaviors (AOB) were conclusive of actual opioid misuse found to be 6.5-24%. Younger age, found in 8/10 studies; personal or family history of anxiety or other mental ill health, found in 6/8 studies; and history of illicit drug use, found in 4/6 studies, showed an increased risk of misuse. CONCLUSIONS: Younger age, personal or familial mental health history, and history of illicit drug use consistently showed an increased risk of opioid misuse. Clinical suspicion of opioid misuse may be raised by data from PMP or any of the standardized list of AOBs. Clinicians may use SOAPP-R, CAGE-AID, or ORT to screen for increased risk and may use UDT to confirm suspicion of opioid misuse or monitor adherence. More research into this important area is required. SIGNIFICANCE OF RESULTS: This systematic review summarized the literature on the use of opioid misuse risk approaches in people with cancer. The rates of reported risk range from 6 to 65%; however, true rate may be closer to 6.5-24%. Younger age, personal or familial mental health history, and history of illicit drug use consistently showed an increased risk of opioid misuse. Clinicians may choose from several approaches. Limited data are available on feasibility and patient experience. PROSPERO registration number. CRD42020163385.

Results from the AAPM Task Group 324 respiratory motion management in radiation oncology survey.

PURPOSE: To quantify the clinical practice of respiratory motion management in radiation oncology. METHODS: A respiratory motion management survey was designed and conducted based on clinician survey guidelines. The survey was administered to American Association of Physicists in Medicine (AAPM) members on 17 August 2020 and closed on 13 September 2020. RESULTS: A total of 527 respondents completed the entire survey and 651 respondents completed part of the survey, with the partially completed surveys included in the analysis. Overall, 84% of survey respondents used deep inspiration breath hold for left-sided breast cancer. Overall, 83% of respondents perceived respiratory motion management for thoracic and abdominal cancer radiotherapy patients to be either very important or required. Overall, 95% of respondents used respiratory motion management for thoracic and abdominal sites, with 36% of respondents using respiratory motion management for at least 90% of thoracic and abdominal patients. The majority (60%) of respondents used the internal target volume method to treat thoracic and abdominal cancer patients, with 25% using breath hold or abdominal compression and 13% using gating or tracking. CONCLUSIONS: A respiratory motion management survey has been completed by AAPM members. Respiratory motion management is generally considered very important or required and is widely used for breast, thoracic, and abdominal cancer treatments.

Study protocol of the LARK (TROG 17.03) clinical trial: a phase II trial investigating the dosimetric impact of Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring.

BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. METHODS: Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. DISCUSSION: Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. TRIAL REGISTRATION: This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .

Real-time high spatial resolution dose verification in stereotactic motion adaptive arc radiotherapy.

PURPOSE: Radiation treatments delivered with real-time multileaf collimator (MLC) tracking currently lack fast pretreatment or real-time quality assurance. The purpose of this study is to test a 2D silicon detector, MagicPlate-512 (MP512), in a complex clinical environment involving real-time reconfiguration of the MLC leaves during target tracking. METHODS: MP512 was placed in the center of a solid water phantom and mounted on a motion platform used to simulate three different patient motions. Electromagnetic target tracking was implemented using the Calypso system (Varian Medical Systems, Palo Alto, CA, USA) and an MLC tracking software. A two-arc VMAT plan was delivered and 2D dose distributions were reconstructed by MP512, EBT3 film, and the Eclipse treatment planning system (TPS). Dose maps were compared using gamma analysis with 2%/2 mm and 3%/3 mm acceptance criteria. Dose profiles were generated in sup-inf and lateral directions to show the agreement of MP512 to EBT3 and to highlight the efficacy of the MLC tracking system in mitigating the effect of the simulated patient motion. RESULTS: Using a 3%/3 mm acceptance criterion for 2D gamma analysis, MP512 to EBT3 film agreement was 99% and MP512 to TPS agreement was 100%. For a 2%/2 mm criterion, the agreement was 95% and 98%, respectively. Full width at half maximum and 80%/20% penumbral width of the MP512 and EBT3 dose profiles agreed within 1 mm and 0.5 mm, respectively. Patient motion increased the measured dose profile penumbral width by nearly 2 mm (with respect to the no-motion case); however, the MLC tracking strategy was able to mitigate 80% of this effect. CONCLUSIONS: MP512 is capable of high spatial resolution 2D dose reconstruction during adaptive MLC tracking, including arc deliveries. It shows potential as an effective tool for 2D small field dosimetry and pretreatment quality assurance for MLC tracking modalities. These results provide confidence that detector-based pretreatment dosimetry is clinically feasible despite fast real-time MLC reconfigurations.

Influence of respiratory motion management technique on radiation pneumonitis risk with robotic stereotactic body radiation therapy.

PURPOSE/OBJECTIVES: For lung stereotactic body radiation therapy (SBRT), real-time tumor tracking (RTT) allows for less radiation to normal lung compared to the internal target volume (ITV) method of respiratory motion management. To quantify the advantage of RTT, we examined the difference in radiation pneumonitis risk between these two techniques using a normal tissue complication probability (NTCP) model. MATERIALS/METHOD: 20 lung SBRT treatment plans using RTT were replanned with the ITV method using respiratory motion information from a 4D-CT image acquired at the original simulation. Risk of symptomatic radiation pneumonitis was calculated for both plans using a previously derived NTCP model. Features available before treatment planning that identified significant increase in NTCP with ITV versus RTT plans were identified. RESULTS: Prescription dose to the planning target volume (PTV) ranged from 22 to 60 Gy in 1-5 fractions. The median tumor diameter was 3.5 cm (range 2.1-5.5 cm) with a median volume of 14.5 mL (range 3.6-59.9 mL). The median increase in PTV volume from RTT to ITV plans was 17.1 mL (range 3.5-72.4 mL), and the median increase in PTV/lung volume ratio was 0.46% (range 0.13-1.98%). Mean lung dose and percentage dose-volumes were significantly higher in ITV plans at all levels tested. The median NTCP was 5.1% for RTT plans and 8.9% for ITV plans, with a median difference of 1.9% (range 0.4-25.5%, pairwise P < 0.001). Increases in NTCP between plans were best predicted by increases in PTV volume and PTV/lung volume ratio. CONCLUSIONS: The use of RTT decreased the risk of radiation pneumonitis in all plans. However, for most patients the risk reduction was minimal. Differences in plan PTV volume and PTV/lung volume ratio may identify patients who would benefit from RTT technique before completing treatment planning.

Stereotactic prostate adaptive radiotherapy utilising kilovoltage intrafraction monitoring: the TROG 15.01 SPARK trial.

BACKGROUND: This paper describes the multi-institutional prospective phase II clinical trial, SPARK: Stereotactic Prostate Adaptive Radiotherapy utilizing Kilovoltage Intrafraction Monitoring (KIM). KIM is a real-time image guided radiotherapy technology being developed and clinically pioneered for prostate cancer treatment in Australia. It has potential for widespread use for target radiotherapy treatment of cancers of the pelvis, thorax and abdomen. METHODS: In the SPARK trial we will measure the cancer targeting accuracy and patient outcomes for 48 prostate cancer patients who will be treated in five treatment sessions as opposed to the conventional 40 sessions. The reduced number of treatment sessions is enabled by the KIM's increased cancer targeting accuracy. DISCUSSION: Real-time imaging in radiotherapy has the potential to decrease the time taken during cancer treatment and reduce the imaging dose required. With the imaging being acquired during the treatment, and the analysis being automated, there is potential for improved throughput. The SPARK trial will be conducted under the auspices of the Trans-Tasman Radiation Oncology Group (TROG). TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov on 09 March 2015. The identifier is: NCT02397317.

Technical note: TROG 15.01 SPARK trial multi-institutional imaging dose measurement.

PURPOSE: The Trans-Tasman Radiation Oncology Group (TROG) 15.01 Stereotactic Prostate Adaptive Radiotherapy utilizing Kilovoltage intrafraction monitoring (SPARK) trial is a multicenter trial using Kilovoltage Intrafraction Monitoring (KIM) to monitor prostate position during the delivery of prostate radiation therapy. KIM increases the accuracy of prostate radiation therapy treatments and allows for hypofractionation. However, an additional imaging dose is delivered to the patient. A standardized procedure to determine the imaging dose per frame delivered using KIM was developed and applied at four radiation therapy centers on three different types of linear accelerator. METHODS: Dose per frame for kilovoltage imaging in fluoroscopy mode was measured in air at isocenter using an ion chamber. Beam quality and dose were determined for a Varian Clinac iX linear accelerator, a Varian Trilogy, four Varian Truebeams and one Elekta Synergy at four different radiation therapy centers. The imaging parameters used on the Varian machines were 125 kV, 80 mA, and 13 ms. The Elekta machine was measured at 120 kV, 80 mA, and 12 ms. Absorbed doses to the skin and the prostate for a typical SBRT prostate treatment length were estimated according to the IPEMB protocol. RESULTS: The average dose per kV frame to the skin was 0.24 ± 0.03 mGy. The average estimated absorbed dose to the prostate for all five treatment fractions across all machines measured was 39.9 ± 2.6 mGy for 1 Hz imaging, 199.7 ± 13.2 mGy for 5 Hz imaging and 439.3 ± 29.0 mGy for 11 Hz imaging. CONCLUSIONS: All machines measured agreed to within 20%. Additional dose to the prostate from using KIM is at most 1.3% of the prescribed dose of 36.25 Gy in five fractions delivered during the trial.

Real-time intrafraction prostate motion during linac based stereotactic radiotherapy with rectal displacement.

BACKGROUND: Kilovoltage Intrafraction Monitoring (KIM) is a method which determines the three-dimensional position of the prostate from two-dimensional kilovoltage (kV) projections taken during linac based radiotherapy treatment with real-time feedback. Rectal displacement devices (RDDs) allow for improved rectal dosimetry during prostate cancer treatment. This study used KIM to perform a preliminary investigation of prostate intrafraction motion observed in patients with an RDD in place. METHODS: Ten patients with intermediate to high-risk prostate cancer were treated with a Rectafix RDD in place during two boost fractions of 9.5-10 Gy delivered using volumetric modulated arc therapy (VMAT) on Clinac iX and Truebeam linacs. Two-dimensional kV projections were acquired during treatment. KIM software was used following treatment to determine the displacement of the prostate over time. The displacement results were analyzed to determine the percentage of treatment time the prostate spent within 1 mm, between 1 and 2 mm, between 2 and 3 mm and greater than 3 mm from its initial position. RESULTS: KIM successfully measured displacement for 19 prostate stereotactic boost fractions. The prostate was within 1 mm of its initial position for 84.8%, 1-2 mm for 14%, 2-3 mm 1.2% and ≥3 mm only 0.4% of the treatment time. CONCLUSIONS: In this preliminary study using KIM, KIM was successfully used to measure prostate intrafraction motion, which was found to be small in the presence of a rectal displacement device. TRIAL REGISTRATION: The Hunter New England Human Research Ethics Committee reference number is 14/08/20/3.01.

An EPID-based system for gantry-resolved MLC quality assurance for VMAT.

Multileaf collimator (MLC) positions should be precisely and independently mea-sured as a function of gantry angle as part of a comprehensive quality assurance (QA) program for volumetric-modulated arc therapy (VMAT). It is also ideal that such a QA program has the ability to relate MLC positional accuracy to patient-specific dosimetry in order to determine the clinical significance of any detected MLC errors. In this work we propose a method to verify individual MLC trajectories during VMAT deliveries for use as a routine linear accelerator QA tool. We also extend this method to reconstruct the 3D patient dose in the treatment planning sys-tem based on the measured MLC trajectories and the original DICOM plan file. The method relies on extracting MLC positions from EPID images acquired at 8.41fps during clinical VMAT deliveries. A gantry angle is automatically tagged to each image in order to obtain the MLC trajectories as a function of gantry angle. This analysis was performed for six clinical VMAT plans acquired at monthly intervals for three months. The measured trajectories for each delivery were compared to the MLC positions from the DICOM plan file. The maximum mean error detected was 0.07 mm and a maximum root-mean-square error was 0.8 mm for any leaf of any delivery. The sensitivity of this system was characterized by introducing random and systematic MLC errors into the test plans. It was demonstrated that the system is capable of detecting random and systematic errors on the range of 1-2mm and single leaf calibration errors of 0.5 mm. The methodology developed in the work has potential to be used for efficient routine linear accelerator MLC QA and pretreatment patient-specific QA and has the ability to relate measured MLC positional errors to 3D dosimetric errors within a patient volume.

Audiovisual biofeedback breathing guidance for lung cancer patients receiving radiotherapy: a multi-institutional phase II randomised clinical trial.

BACKGROUND: There is a clear link between irregular breathing and errors in medical imaging and radiation treatment. The audiovisual biofeedback system is an advanced form of respiratory guidance that has previously demonstrated to facilitate regular patient breathing. The clinical benefits of audiovisual biofeedback will be investigated in an upcoming multi-institutional, randomised, and stratified clinical trial recruiting a total of 75 lung cancer patients undergoing radiation therapy. METHODS/DESIGN: To comprehensively perform a clinical evaluation of the audiovisual biofeedback system, a multi-institutional study will be performed. Our methodological framework will be based on the widely used Technology Acceptance Model, which gives qualitative scales for two specific variables, perceived usefulness and perceived ease of use, which are fundamental determinants for user acceptance. A total of 75 lung cancer patients will be recruited across seven radiation oncology departments across Australia. Patients will be randomised in a 2:1 ratio, with 2/3 of the patients being recruited into the intervention arm and 1/3 in the control arm. 2:1 randomisation is appropriate as within the interventional arm there is a screening procedure where only patients whose breathing is more regular with audiovisual biofeedback will continue to use this system for their imaging and treatment procedures. Patients within the intervention arm whose free breathing is more regular than audiovisual biofeedback in the screen procedure will remain in the intervention arm of the study but their imaging and treatment procedures will be performed without audiovisual biofeedback. Patients will also be stratified by treating institution and for treatment intent (palliative vs. radical) to ensure similar balance in the arms across the sites. Patients and hospital staff operating the audiovisual biofeedback system will complete questionnaires to assess their experience with audiovisual biofeedback. The objectives of this clinical trial is to assess the impact of audiovisual biofeedback on breathing motion, the patient experience and clinical confidence in the system, clinical workflow, treatment margins, and toxicity outcomes. DISCUSSION: This clinical trial marks an important milestone in breathing guidance studies as it will be the first randomised, controlled trial providing the most comprehensive evaluation of the clinical impact of breathing guidance on cancer radiation therapy to date. This study is powered to determine the impact of AV biofeedback on breathing regularity and medical image quality. Objectives such as determining the indications and contra-indications for the use of AV biofeedback, evaluation of patient experience, radiation toxicity occurrence and severity, and clinician confidence will shed light on the design of future phase III clinical trials. TRIAL REGISTRATION: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), its trial ID is ACTRN12613001177741 .

Data-driven rapid 4D cone-beam CT reconstruction for new generation linacs.

Objective.Newer generation linear accelerators (Linacs) allow 20 s cone-beam CT (CBCT) acquisition which reduces radiation therapy treatment time. However, the current clinical application of these rapid scans is only 3DCBCT. In this paper we propose a novel data-driven rapid 4DCBCT reconstruction method for new generation linacs.Approach.This method relies on estimating the magnitude of the diaphragm motion from an initial 3D reconstruction. This estimated motion is used to linearly approximate a deformation vector field (DVF) for each respiration phase. These DVFs are then used for motion compensated Feldkamp-Davis-Kress (MCFDK) reconstructions. This method, named MCFDK Data Driven (MCFDK-DD), was compared to a MCFDK reconstruction using a prior motion model (MCFDK-Prior), a 3D-FDK reconstruction, and a conventional acquisition (4 mins) conventional reconstruction 4DCBCT (4D-FDK). The data used in this paper were derived from 4DCT volumes from 12 patients from The Cancer Imaging Archives. Image quality was quantified using RMSE of line plots centred on the tumour, tissue interface width (TIW), the mean square error (MSE) and structural similarity index measurement (SSIM).Main Results.The tumour line plots in the Superior-Inferior direction showed reduced RMSE for the MCFDK-DD compared to the 3D-FDK method, indicating the MCFDK-DD method provided a more accurate tumour location. Similarly, the TIW values from the MCFDK-DD reconstructions (median 8.6 mm) were significantly reduced for the MCFDK-DD method compared to the 3D-FDK reconstructions (median 14.8 mm, (p< 0.001). The MCFDK-DD, MCFDK-Prior and 3D-FDK had median MSE values of1.08×10-6mm-1,1.11×10-6mm-1and1.17×10-6mm-1respectively. The corresponding median SSIM values were 0.93, 0.92 and 0.92 respectively indicating the MCFDK-DD had good agreement with the conventional 4D-FDK reconstructions.Significance.These results demonstrate the feasibility of creating accurate data-driven 4DCBCT images for rapid scans on new generation linacs. These findings could lead to increased clinical usage of 4D information on newer generation linacs.

The Remove-the-Mask Open-Source head and neck Surface-Guided radiation therapy system.

Background and Purpose: Surface Guided Radiotherapy (SGRT) for head and neck radiotherapy is challenging as obstructions are common and non-rigid facial motion can compromise surface accuracy. The purpose of this work was to develop and benchmark the Remove the Mask (RtM) SGRT system, an open-source system especially designed to address the challenges faced in radiotherapy of head and neck cancer. Materials and Methods: The accuracy of the RtM SGRT system was benchmarked using a head phantom positioned on a robotic motion platform capable of sub-millimetre accuracy which was used to induce unidirectional shifts and to reproduce three real head motion traces. We also assessed the accuracy of the system in ten humans volunteers. The ground truth motion of the volunteers was obtained using a commercial motion capture system with an accuracy < 0.3 mm. Results: The mean tracking error of the RtM SGRT system for the ten volunteers was of -0.1 ± 0.4 mm -0.6 ± 0.6 mm and 0.3 ± 0.2 mm, and 0.0 ± 0.2° 0.0 ± 0.1° and 0.0 ± 0.2° for translations and rotations along the left-right, superior-inferior and anterior-posterior axes respectively and we also found similar results in measurements with the head phantom. Forced facial motion was associated with lower tracking accuracy. The RtM SGRT system achieved submillimetre accuracy. Conclusion: The RtM SGRT system is a low-cost, easy to build and open-source SGRT system that can achieve an accuracy that meets international commissioning guidelines. Its open-source and modular design allows for the development and easy translation of novel surface tracking techniques.

Radiotherapy protocol compliance in routine clinical practice for patients with stages I-III non-small-cell lung cancer.

INTRODUCTION: Despite the availability of radiotherapy treatment protocols for lung cancer, considerable treatment variation occurs in clinical practice. This study assessed compliance with a radiotherapy protocol for the treatment of patients with stages I-III non-small-cell lung cancer (NSCLC) in routine clinical practice and to identify factors that were associated with compliance. METHODS: The Cancer Institute New South Wales eviQ treatment protocol for external beam radiotherapy of stages I-III NSCLC was taken as the reference to measure compliance. All inoperable patients with stages I-III NSCLC and documented ECOG performance status treated with radiotherapy between 2007 and 2019 at two radiotherapy facilities were available for analysis. Protocol compliance rates were calculated. Univariate and multivariate logistic regression models with 23 input factors were used to determine factors significantly associated with compliance. Survival analysis was conducted for both compliant and non-compliant treatments. RESULTS: Overall, 656 patients met the inclusion criteria. Protocol compliance was 16%. Alternative dose/fractionation was responsible for 49% of non-compliant treatments with 30% receiving an alternative curative fractionation. Five of 23 factors (age at the start of radiotherapy, stage group, ECOG performance status, tumour location and alcoholism history) showed significant associations with protocol compliance on multivariate analysis. There was no significant difference in median survival between patients receiving protocol compliant treatment (15.1 months) and non-compliant treatment (15.6 months). CONCLUSION: Adherence to the eviQ curative radiotherapy protocol for stages I-III NSCLC was low. Alternative dose/fractionation schemes were the main reason for non-compliance. Protocol compliance was not associated with outcome.

Overview of cardiac toxicity from radiation therapy.

Radiotherapy is an essential part of treatment for many patients with thoracic cancers. However, proximity of the heart to tumour targets can lead to cardiac side effects, with studies demonstrating link between cardiac radiation dose and adverse outcomes. Although reducing cardiac dose can reduce associated risks, most cardiac constraint recommendations in clinical use are generally based on dose to the whole heart, as dose assessment at cardiac substructure levels on individual patients has been limited historically. Furthermore, estimation of an individual's cardiac risk is complex and multifactorial, which includes radiation dose alongside baseline risk factors, and the impact of systemic therapies. This review gives an overview of the epidemiological impact of cancer and cardiac disease, risk factors contributing to radiation-related cardiotoxicity, the evidence for cardiac side effects and future directions in cardiotoxicity research. A better understanding of the interactions between risk factors, balancing treatment benefit versus toxicity and the ongoing management of cardiac risk is essential for optimal clinical care. The emerging field of cardio-oncology is thus a multidisciplinary collaborative effort to enable better understanding of cardiac risks and outcomes for better-informed patient management decisions.

Super-resolution neural networks improve the spatiotemporal resolution of adaptive MRI-guided radiation therapy.

BACKGROUND: Magnetic resonance imaging (MRI) offers superb non-invasive, soft tissue imaging of the human body. However, extensive data sampling requirements severely restrict the spatiotemporal resolution achievable with MRI. This limits the modality's utility in real-time guidance applications, particularly for the rapidly growing MRI-guided radiation therapy approach to cancer treatment. Recent advances in artificial intelligence (AI) could reduce the trade-off between the spatial and the temporal resolution of MRI, thus increasing the clinical utility of the imaging modality. METHODS: We trained deep learning-based super-resolution neural networks to increase the spatial resolution of real-time MRI. We developed a framework to integrate neural networks directly onto a 1.0 T MRI-linac enabling real-time super-resolution imaging. We integrated this framework with the targeting system of the MRI-linac to demonstrate real-time beam adaptation with super-resolution-based imaging. We tested the integrated system using large publicly available datasets, healthy volunteer imaging, phantom imaging, and beam tracking experiments using bicubic interpolation as a baseline comparison. RESULTS: Deep learning-based super-resolution increases the spatial resolution of real-time MRI across a variety of experiments, offering measured performance benefits compared to bicubic interpolation. The temporal resolution is not compromised as measured by a real-time adaptation latency experiment. These two effects, an increase in the spatial resolution with a negligible decrease in the temporal resolution, leads to a net increase in the spatiotemporal resolution. CONCLUSIONS: Deployed super-resolution neural networks can increase the spatiotemporal resolution of real-time MRI. This has applications to domains such as MRI-guided radiation therapy and interventional procedures.

Magnetic resonance imaging (MRI) is a medical imaging modality that is used to image organs such as the brain, lungs, and liver as well as diseases such as cancer. MRI scans taken at high resolution are of overly long duration. This time constraint limits the accuracy of MRI-guided cancer radiation therapy, where imaging must be fast to adapt treatment to tumour motion. Here, we deployed artificial intelligence (AI) models to achieve fast and high detail MRI. We additionally validated our AI models across various scenarios. These AI-based models could potentially enable people with cancer to be treated with higher accuracy and precision.

Six-degrees-of-freedom pelvic bone monitoring on 2D kV intrafraction images to enable multi-target tracking for locally advanced prostate cancer.

BACKGROUND: Patients with locally advanced prostate cancer require the prostate and pelvic lymph nodes to be irradiated simultaneously during radiation therapy treatment. However, relative motion between treatment targets decreases dosimetric conformity. Current treatment methods mitigate this error by having large treatment margins and often prioritize the prostate at patient setup at the cost of lymph node coverage. PURPOSE: Treatment accuracy can be improved through real-time multi-target adaptation which requires simultaneous motion monitoring of both the prostate and lymph node targets. This study developed and evaluated an intrafraction pelvic bone motion monitoring method as a surrogate for pelvic lymph node displacement to be combined with prostate motion monitoring to enable multi-target six-degrees-of-freedom (6DoF) tracking using 2D kV projections acquired during treatment. MATERIAL AND METHODS: A method to monitor pelvic bone translation and rotation was developed and retrospectively applied to images from 20 patients treated in the TROG 15.01 Stereotactic Prostate Ablative Radiotherapy with Kilovoltage Intrafraction Monitoring (KIM) trial. The pelvic motion monitoring method performed template matching to calculate the 6DoF position of the pelvis from 2D kV images. The method first generated a library of digitally reconstructed radiographs (DRRs) for a range of imaging angles and pelvic rotations. The normalized 2D cross-correlations were then calculated for each incoming kV image and a subset of DRRs and the DRR with the maximum correlation coefficient was used to estimate the pelvis translation and rotation. Translation of the pelvis in the unresolved direction was calculated using a 3D Gaussian probability estimation method. Prostate motion was measured using the KIM marker tracking method. The pelvic motion monitoring method was compared to the ground truth obtained from a 6DoF rigid registration of the CBCT and CT. RESULTS: The geometric errors of the pelvic motion monitoring method demonstrated sub-mm and sub-degree accuracy and precision in the translational directions ( T LR ${{T}_{{\mathrm{LR}}}}$ , T SI ${{T}_{{\mathrm{SI}}}}$ , T AP ${{T}_{{\mathrm{AP}}}}$ ) and rotational directions ( R LR ${{R}_{{\mathrm{LR}}}}$ , R SI ${{R}_{{\mathrm{SI}}}}$ , R AP ${{R}_{{\mathrm{AP}}}}$ ). The 3D relative displacement between the prostate and pelvic bones exceeded 2, 3, 5, and 7 mm for approximately 66%, 44%, 12%, and 7% of the images. CONCLUSIONS: Accurate intrafraction pelvic bone motion monitoring in 6DoF was demonstrated on 2D kV images, providing a necessary tool for real-time multi-target motion-adapted treatment.

Open-source hardware and software for the measurement, characterization, reporting, and correction of geometric distortion in MRI.

BACKGROUND: Geometric distortion is a serious problem in MRI, particularly in MRI guided therapy. A lack of affordable and adaptable tools in this area limits research progress and harmonized quality assurance. PURPOSE: To develop and test a suite of open-source hardware and software tools for the measurement, characterization, reporting, and correction of geometric distortion in MRI. METHODS: An open-source python library was developed, comprising modules for parametric phantom design, data processing, spherical harmonics, distortion correction, and interactive reporting. The code was used to design and manufacture a distortion phantom consisting of 618 oil filled markers covering a sphere of radius 150 mm. This phantom was imaged on a CT scanner and a novel split-bore 1.0 T MRI magnet. The CT images provide distortion-free dataset. These data were used to test all modules of the open-source software. RESULTS: All markers were successfully extracted from all images. The distorted MRI markers were mapped to undistorted CT data using an iterative search approach. Spherical harmonics reconstructed the fitted gradient data to 1.0 ± 0.6% of the input data. High resolution data were reconstructed via spherical harmonics and used to generate an interactive report. Finally, distortion correction on an independent data set reduced distortion inside the DSV from 5.5 ± 3.1 to 1.6 ± 0.8 mm. CONCLUSION: Open-source hardware and software for the measurement, characterization, reporting, and correction of geometric distortion in MRI have been developed. The utility of these tools has been demonstrated via their application on a novel 1.0 T split bore magnet.